Mixed Chimerism of the Resident Macrophage Population After Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia1

Wickenhauser, Claudia; Thiele, Jüergen; Pérez, Fernando Guerrero; Varus, E.; Stoffel, Marc Sebastian; Kvasnicka, Hans Michael; Beelen, Dietrich W.; Schaefer, U.W.

doi:10.1097/00007890-200201150-00020

Cited by 15 publications

(13 citation statements)

References 38 publications

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“…4,6 This is supported by the observation in chronic myelogenous leukemia that the macrophage population remains chimeric until 3 months after allo-HSCT, even when myeloablative conditioning regimens (including total body irradiation) are employed. 8 We conclude that host-derived macrophages were involved in the development of the early onset-allo-HSCT-associated HPS as a form of host-versus-graft response, and that this may induce graft rejection. However, given that JMML is a myelomonocytic proliferative disease and that patients with JMML are therefore predisposed to develop HPS, 9,10 it remains possible that our observation is only pertinent for JMML.…”

mentioning

confidence: 73%

Origin of macrophages involved in the development of allogeneic hematopoietic stem cell transplantation-associated hemophagocytic syndrome: observations on a patient with juvenile myelomonocytic leukemia

Ishida

Yoshida

Yoshihara

et al. 2007

Bone Marrow Transplant

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mentioning

confidence: 73%

Origin of macrophages involved in the development of allogeneic hematopoietic stem cell transplantation-associated hemophagocytic syndrome: observations on a patient with juvenile myelomonocytic leukemia

Ishida

Yoshida

Yoshihara

et al. 2007

Bone Marrow Transplant

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“…23 Similarly, humans that undergo allogeneic BM transplantation after myeloablative-conditioning regimens have mixed AM chimerism. 24,25 A key question that arises from each of these settings is whether AMs with different ontogeny (ie, embryonic-derived vs postnatal-derived monocytes) exhibit similar or differential phenotypes and functions, and whether the environment of the pulmonary airspaces is dominant in The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.…”

mentioning

confidence: 99%

Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages

Gibbings

Goyal

Desch³

et al. 2015

Blood

200

188

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• Of the 30 000 genes, there are ;0.1% genes whose expression is linked to the origin of the cell rather than the environment.• Marco was most conserved by embryonic origin and not altered by the environment, whereas C1qb and Plbd1 were most conserved by adult origin.Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and alveoli where they maintain host defense and promote alveolar homeostasis by ingesting inhaled particulates and regulating inflammatory responses. Recent studies have demonstrated that AMs populate the lungs during embryogenesis and self-renew throughout life with minimal replacement by circulating monocytes, except under extreme conditions of depletion or radiation injury. Here we demonstrate that on a global scale, environment appears to dictate AM development and function. Indeed, transcriptome analysis of embryonic host-derived and postnatal donor-derived AMs coexisting within the same mouse demonstrated >98% correlation and overall functional analyses were similar. However, we also identified several genes whose expression was dictated by origin rather than environment. The most differentially expressed gene not altered by environment was Marco, a gene recently demonstrated to have enhancer activity in embryonic-derived but not postnatal-derived tissue macrophages. Overall, we show that under homeostatic conditions, the environment largely dictates the programming and function of AMs, whereas the expression of a small number of genes remains linked to the origin of the cell. (Blood. 2015;126(11):1357-1366 Introduction Alveolar macrophages (AMs) reside on the luminal surfaces of the airways and airspaces where they serve critical roles in host defense and alveolar homeostasis, ingesting particulates and microbes that are constantly encountered in the lungs. Importantly, under most circumstances the phagocytosis of inhaled foreign agents is silent, such that inflammatory responses are activated only under circumstances when host defenses become overwhelmed.1 Indeed, compared with macrophages from other sites, AMs are relatively ineffective at initiating immune responses.2,3 Furthermore, compared with other tissue macrophages, they display a unique repertoire of cell surface molecules and have a distinct transcriptome profile. [4][5][6] AMs are now known to derive primarily from fetal liver monocytes and self-renew throughout life with minimal replenishment from circulating monocytes. [7][8][9][10][11][12][13][14][15] This self-renewal is not only maintained under steady-state conditions, but also during acute and chronic inflammation.16 These concepts were illustrated in lung-protected bone marrow (BM) chimera studies in which lead shields were used to protect AMs during radiation. Eight weeks after BM transplantation, the lungs of these chimeras contained AMs of host origin, whereas circulating monocytes were donor-derived. 16 In these chimeric mice, we showed that during inflammation (lipopolysaccharide or influenza A infection), BM donor-derived monocytes were rapidly...

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“…However, it has to be considered that the number of host cells does not necessarily reflect the number of neoplastic hematopoiesis (17,18,20) and the relevance of host cell number on HCT outcome remains controversial (27)(28)(29)(30). Analyzing the same BM biopsies, we reported a BCR/ABL positive population within the CD34 + cell compartment ranging from 5 to 10% (18) indicating that 30-50% of the host CD34 + cells bear the translocation.…”

Section: Discussionmentioning

confidence: 90%

“…Subsequently, the slides were incubated with a satellite probe mix for chromosomes x and y (CEP X Spectrum Orange/CEP Y Spectrum Green DNA Probe Kit; Vysis, Bergisch Gladbach, Germany) as described previously (20).…”

Section: Sequential Immunostaining and Dual Color Fluorescence In Sitmentioning

confidence: 99%

Differences in proportion and dynamics of recipient hematopoiesis following hematopoietic cell transplantation in CML and IMF

Siebolts

Thiele²,

Zander³

et al. 2008

Oncol Rep

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Abstract. Since decades myeloablation followed by allogeneic stem cell transplantation offered the only opportunity to cure leukemia patients and only recently the development of STI571 created a further alternative in chronic myeloid leukemia (CML). While among all leukemias this transplantation regimen had the best outcome in CML, trials with reduced intensity conditioning regimens (RIC) were rather humbling and recurrence of the neoplastic clone occurred frequently. However, the same therapy in patients with idiopathic myelofibrosis (IMF) resulted in a more favorable outcome. Therefore, long-term mixed chimerism (mCh) was determined on bone marrow (BM) biopsies derived from five IMF patients and from eight CML patients of the pre STI era following sex-mismatched transplantation. All patients presented lasting hematologic remission and were matched concerning age, sex and appearance of GvHD. Analysis of late transplant period (day +100) revealed a concentration of host cells within the CD34 + precursor cell compartment in both diseases. However, in IMF BM biopsies only up to 8% recipient CD34 + precursors but in CML biopsies up to 26% recipient CD34 + precursors were detected. Taken into account that in CML up to 10% of the host BM CD34 + precursors bear the BCR-ABL translocation our data suggest that the neoplastic CD34 + progenitor cell population might dispose of better strategies to escape immune surveillance in CML than in IMF.

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Mixed Chimerism of the Resident Macrophage Population After Allogeneic Bone Marrow Transplantation for Chronic Myeloid Leukemia1

Abstract: The CD68+ resident bone marrow macrophage population including PGCs are involved in the lineage-specific chimerism and minimal residual disease after BMT in CML.

Cited by 15 publications

References 38 publications

Origin of macrophages involved in the development of allogeneic hematopoietic stem cell transplantation-associated hemophagocytic syndrome: observations on a patient with juvenile myelomonocytic leukemia

Origin of macrophages involved in the development of allogeneic hematopoietic stem cell transplantation-associated hemophagocytic syndrome: observations on a patient with juvenile myelomonocytic leukemia

Transcriptome analysis highlights the conserved difference between embryonic and postnatal-derived alveolar macrophages

Differences in proportion and dynamics of recipient hematopoiesis following hematopoietic cell transplantation in CML and IMF

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